Fas Ligand Engagement of Resident Peritoneal Macrophages In Vivo Induces Apoptosis and the Production of Neutrophil Chemotactic Factors

Hohlbaum, Andreas M.; Gregory, Meredith S.; Ju, Shyr‐Te; Marshak‐Rothstein, Ann

doi:10.4049/jimmunol.167.11.6217

Cited by 141 publications

(156 citation statements)

References 50 publications

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“…It has been reported that CD95L induces the processing and release of IL-1 g , which may be responsible for the infiltration by neutrophils [41]. CD95L may act on resident macrophages leading to increased production of IL-1 g and macrophage inflammatory proteins [42]. Moreover, engagement of CD95 on dendritic cells may induce the secretion of pro-inflammatory cytokines [43].…”

Section: Discussionmentioning

confidence: 99%

The influence of CD95L expression on tumor rejection in mice

Igney¹,

Behrens²,

Krammer³

2003

Eur J Immunol

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Many tumors express the death ligand CD95L (CD178, APO-1L, FasL) and can kill activated T cells in vitro. This may enable the tumor cells to suppress anti-tumor immune responses, a phenomenon called "tumor counterattack". Preliminary evidence of tumor counterattack in human tumors exists. However, CD95L-expressing tumors are rapidly rejected in mice. In order to clarify this controversial situation we investigated whether the level or the time point of CD95L expression might be critical factors determining tumor counterattack versus tumor rejection. We generated CD95-resistant tumor cell lines expressing different levels of CD95L (LKC-CD95L). In nude mice the CD95L expression level had no influence on the growth of the CD95L + tumors. In contrast, a CD95L -control tumor cell line (LKC) grew much faster. In addition, we generated a CD95-resistant cell line in which CD95L was induced via the tet system (LKCR-tetCD95L). Induction of CD95L in established tumors in nude and NOD/SCID mice led to rapid rejection of the tumors. Induction of lower CD95L expression levels delayed tumor rejection only marginally. These results demonstrate that rejection of CD95L-expressing tumors in mice is not a result of overexpression and does not depend on the presence of CD95L at the onset of tumor progression.

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Section: Discussionmentioning

confidence: 99%

The influence of CD95L expression on tumor rejection in mice

Igney¹,

Behrens²,

Krammer³

2003

Eur J Immunol

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“…11,[39][40][41] These effector cells may directly kill Fas-expressing hepatocytes. 39 Alternatively, Fas-FasL crosslinking between innate immune cells and target cells such as hepatocytes, or even among the innate immune cells themselves within the liver, may have a pro-inflamamtory activity by inducing inflammatory cytokines/ chemokines, 11,[42][43][44][45] thereby aggravating APAP-induced liver injury. In the current study, we observed a marked reduction of FasL-expressing hepatic leukocytes in neutrophil-depleted mice compared with that in APAPtreated control mice, suggesting that neutrophils are important FasL-expressing cells in the liver and may contribute to APAP-induced liver injury through Fas/FasL pathways.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil depletion protects against murine acetaminophen hepatotoxicity

et al. 2006

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We previously reported that liver natural killer (NK) and NKT cells play a critical role in mouse model of acetaminophen (APAP)-induced liver injury by producing interferon gamma (IFN-␥) and modulating chemokine production and subsequent recruitment of neutrophils into the liver. In this report, we examined the role of neutrophils in the progression of APAP hepatotoxicity. C57BL/6 mice were given an intraperitoneal toxic dose of APAP (500 mg/kg), which caused severe acute liver injury characterized by significant elevation of serum ALT, centrilobular hepatic necrosis, and increased hepatic inflammatory cell accumulation. Flow cytometric analysis of isolated hepatic leukocytes demonstrated that the major fraction of increased hepatic leukocytes at 6 and 24 hours after APAP was neutrophils (Mac-1 ؉ Gr-1 ؉ ). Depletion of neutrophils by in vivo treatment with anti-Gr-1 antibody (RB6-8C5) significantly protected mice against APAP-induced liver injury, as evidenced by markedly reduced serum ALT levels, centrilobular hepatic necrosis, and improved mouse survival. The protection was associated with decreased FasL-expressing cells, cytotoxicity against hepatocytes, and respiratory burst in hepatic leukocytes. In intracellular adhesion molecule (ICAM)-1-deficient mice, APAP caused markedly reduced liver injury when compared with wild-type mice. The marked protection in ICAM-1-deficient mice was associated with decreased accumulation of neutrophils in the liver. Hepatic GSH depletion and APAP-adducts showed no differences among the antibody-treated, ICAM-1-deficient, and normal mice. In conclusion, accumulated neutrophils in the liver contribute to the progression and severity of APAP-induced liver injury. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

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“…The Fas/FasL-mediated apoptosis pathway has been implicated in immune response regulation (9,10), peripheral tolerance (5,(11)(12)(13)(14)(15), graft rejection (16 -18), tumor surveillance (19), tissue pathology (20 -22), chemotaxis (17,18,23), and maintenance of the immune privileged sites (24,25).…”

Section: F As (Cd95) Is a Type I Transmembrane Protein Expressed By Mmentioning

confidence: 99%

Novel Negative Regulator of Expression in Fas Ligand (CD178) Cytoplasmic Tail: Evidence for Translational Regulation and against Fas Ligand Retention in Secretory Lysosomes

Xiao

Deshmukh

Jodo

et al. 2004

The Journal of Immunology

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Fas ligand ((FasL) CD178), a type II transmembrane protein, induces apoptosis of cells expressing the Fas receptor. It possesses a unique cytoplasmic tail (FasLCyt) of 80 aa. As a type II transmembrane protein, the early synthesis of FasLCyt could affect FasL translation by impacting FasL endoplasmic reticulum translocation and/or endoplasmic reticulum retention. Previous studies suggest that the proline-rich domain (aa 43–70) in FasLCyt (FasLPRD) inhibits FasL membrane expression by retaining FasL in the secretory lysosomes. This report shows that deletion of aa 2–33 of FasLCyt dramatically increased total FasL levels and FasL cell surface expression. This negative regulator of FasL expression is dominant despite the presence of FasLPRD. In addition, retention of proline-rich domain-containing FasL in the cytoplasm was not observed. Moreover, we demonstrated that FasLCyt regulates FasL expression by controlling the rate of de novo synthesis of FasL. Our study demonstrated a novel negative regulator of FasL expression in the FasLCyt region and its mechanism of action.

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Fas Ligand Engagement of Resident Peritoneal Macrophages In Vivo Induces Apoptosis and the Production of Neutrophil Chemotactic Factors

Cited by 141 publications

References 50 publications

The influence of CD95L expression on tumor rejection in mice

The influence of CD95L expression on tumor rejection in mice

Neutrophil depletion protects against murine acetaminophen hepatotoxicity

Novel Negative Regulator of Expression in Fas Ligand (CD178) Cytoplasmic Tail: Evidence for Translational Regulation and against Fas Ligand Retention in Secretory Lysosomes

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